Olfactory neurons and taste cells are continuously replaced throughout life. Chemosensory systems, therefore, have evolved unique cellular and molecular strategies to maintain their functional integrity. The capacity to reinnervate the adult mammalian CNS is unique to olfactory neurons. Olfactory neurons induce the development and maintain the expression of transmitter phenotypes in the olfactory bulb. The initial induction and continued development of the bulb may be trophically dependent on neurons and other cells of the olfactory placode. Gustatory nerves induce and trophically maintain taste cells. The seven projects of this program focus on these unique developmental, regenerative and trophic properties of chemosensory cells. Novel hypotheses of the specific molecular and cell-cell interactions that regulate the expression of these unique properties will be tested. The Program has matured from its phenomenological, technique-driven beginnings to a hypothesis-based experiment-driven stage. Inter-project collaborations are far more extensive than four years ago. Antibodies and gene probes will be used to pinpoint hypothesized sequences of cell-cell, and cell-molecular interactions which underlie similarities and differences among development, turnover and regeneration of olfactory and taste cells. Neural transplants and tissue culture systems will pit olfactory cells and molecules against non-olfactory cells and molecules to determine whether the factors that specify pathway development, or permit reinnervation are unique to chemosensory cells or are properties expressed by other cells at certain stages of their development. Cell and ciliary patch and intracellular recording techniques will define the development of channels and membrane coupling events that are associated with maturation of transduction processes in cultured and dissociated cells. Immunoelectron microscope analysis of recently characterized transduction- coupling molecules will be coordinated with the membrane biophysical studies. Newly discovered genetic mutants, neural transplantation and tissue culture methods will be used to determine the specificity and molecular bases of olfactory nerve trophic actions on the development of the bulb and its transmitter phenotypes. Similar approaches will be used to isolate the role of bulb cells in the functional maturation of olfactory neurons. Understanding the developmental and regenerative strategies evolved to cope with receptor turnover, is one of the fundamental goals of chemosensory neuroscience. Achievement of this goal may provide new direction to the prevention and treatment of developmental and degenerative disorders in other parts of the CNS.